Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Frequent lack of repressive capacity of promoter DNA methylation identified through genome-wide epigenomic manipulation

View ORCID ProfileEthan Ford, View ORCID ProfileMatthew R. Grimmer, View ORCID ProfileSabine Stolzenburg, View ORCID ProfileOzren Bogdanovic, View ORCID ProfileAlex de Mendoza, View ORCID ProfilePeggy J. Farnham, View ORCID ProfilePilar Blancafort, View ORCID ProfileRyan Lister
doi: https://doi.org/10.1101/170506
Ethan Ford
1Australian Research Council Centre of Excellence in Plant Energy Biology, School of Molecular Sciences, The University of Western Australia, 35 Stirling Hwy, Crawley, WA 6009, Australia.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Ethan Ford
Matthew R. Grimmer
2Department of Biochemistry and Molecular Medicine, University of Southern California, 1450 Biggy St, Los Angeles, CA 90089, USA.
3 Integrated Genetics and Genomics, University of California, Davis, 451 Health Sciences Dr, Davis, CA 95616, USA.
4Department of Neurological Surgery, University of California, San Francisco, 1450 3rd St, San Francisco, CA 94158, USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Matthew R. Grimmer
Sabine Stolzenburg
5School of Anatomy, Physiology and Human Biology, The University of Western Australia, 35 Stirling Hwy, Crawley, WA 6009, Australia.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Sabine Stolzenburg
Ozren Bogdanovic
1Australian Research Council Centre of Excellence in Plant Energy Biology, School of Molecular Sciences, The University of Western Australia, 35 Stirling Hwy, Crawley, WA 6009, Australia.
6Genomics and Epigenetics Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
7St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Ozren Bogdanovic
Alex de Mendoza
1Australian Research Council Centre of Excellence in Plant Energy Biology, School of Molecular Sciences, The University of Western Australia, 35 Stirling Hwy, Crawley, WA 6009, Australia.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Alex de Mendoza
Peggy J. Farnham
2Department of Biochemistry and Molecular Medicine, University of Southern California, 1450 Biggy St, Los Angeles, CA 90089, USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Peggy J. Farnham
Pilar Blancafort
5School of Anatomy, Physiology and Human Biology, The University of Western Australia, 35 Stirling Hwy, Crawley, WA 6009, Australia.
8Harry Perkins Institute of Medical Research, 6 Verdun St, Nedlands, WA 6009, Australia.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Pilar Blancafort
Ryan Lister
1Australian Research Council Centre of Excellence in Plant Energy Biology, School of Molecular Sciences, The University of Western Australia, 35 Stirling Hwy, Crawley, WA 6009, Australia.
8Harry Perkins Institute of Medical Research, 6 Verdun St, Nedlands, WA 6009, Australia.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Ryan Lister
  • For correspondence: ryan.lister@uwa.edu.au
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

It is widely assumed that the addition of DNA methylation at CpG rich gene promoters silences gene transcription. However, this conclusion is largely drawn from the observation that promoter DNA methylation inversely correlates with gene expression in natural conditions. The effect of induced DNA methylation on endogenous promoters has yet to be comprehensively assessed. Here, we induced the simultaneous methylation of thousands of promoters in the genome of human cells using an engineered zinc finger-DNMT3A fusion protein, enabling assessment of the effect of forced DNA methylation upon transcription, histone modifications, and DNA methylation persistence after the removal of the fusion protein. We find that DNA methylation is frequently insufficient to transcriptionally repress promoters. Furthermore, DNA methylation deposited at promoter regions associated with H3K4me3 is rapidly erased after removal of the zinc finger-DNMT3A fusion protein. Finally, we demonstrate that induced DNA methylation can exist simultaneously on promoter nucleosomes that possess the active histone modification H3K4me3, or DNA bound by the initiated form of RNA polymerase II. These findings suggest that promoter DNA methylation is not generally sufficient for transcriptional inactivation, with implications for the emerging field of epigenome engineering.

One Sentence Summary Genome-wide epigenomic manipulation of thousands of human promoters reveals that induced promoter DNA methylation is unstable and frequently does not function as a primary instructive biochemical signal for gene silencing and chromatin reconfiguration.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted September 20, 2017.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Frequent lack of repressive capacity of promoter DNA methylation identified through genome-wide epigenomic manipulation
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Frequent lack of repressive capacity of promoter DNA methylation identified through genome-wide epigenomic manipulation
Ethan Ford, Matthew R. Grimmer, Sabine Stolzenburg, Ozren Bogdanovic, Alex de Mendoza, Peggy J. Farnham, Pilar Blancafort, Ryan Lister
bioRxiv 170506; doi: https://doi.org/10.1101/170506
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Frequent lack of repressive capacity of promoter DNA methylation identified through genome-wide epigenomic manipulation
Ethan Ford, Matthew R. Grimmer, Sabine Stolzenburg, Ozren Bogdanovic, Alex de Mendoza, Peggy J. Farnham, Pilar Blancafort, Ryan Lister
bioRxiv 170506; doi: https://doi.org/10.1101/170506

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Genomics
Subject Areas
All Articles
  • Animal Behavior and Cognition (3505)
  • Biochemistry (7346)
  • Bioengineering (5323)
  • Bioinformatics (20260)
  • Biophysics (10016)
  • Cancer Biology (7743)
  • Cell Biology (11300)
  • Clinical Trials (138)
  • Developmental Biology (6437)
  • Ecology (9951)
  • Epidemiology (2065)
  • Evolutionary Biology (13321)
  • Genetics (9361)
  • Genomics (12583)
  • Immunology (7701)
  • Microbiology (19021)
  • Molecular Biology (7441)
  • Neuroscience (41036)
  • Paleontology (300)
  • Pathology (1229)
  • Pharmacology and Toxicology (2137)
  • Physiology (3160)
  • Plant Biology (6860)
  • Scientific Communication and Education (1272)
  • Synthetic Biology (1896)
  • Systems Biology (5311)
  • Zoology (1089)